Lipoproteins such as high density lipoprotein (HDL) and low density lipoprotein (LDL) are commonly studied in both epidemiological and genetic studies. However, their simple classification undermines the complexity of these lipoproteins with respect to size, composition and roles in metabolic pathways. For example, results for the association between HDL and coronary heart disease (CHD) are mixed with regards to the direction of effect. Conversely, the association between genetic variants associated with LDL and CHD appear to be much more uniform. Therefore, If HDL is to be regarded as a valid biomarker for drug targets, all genetic variants associated with HDL should have a corresponding consistent effect.
To date, studies may lack power to determine the effect of HDL on CHD. In addition, HDL-C as conventionally measured may not be sufficient biomarker to allow associations to be revealed. Therefore, before discarding the potential of the HDL to CHD, it is worth considering additional biomarkers that better characterise the full complexity of the pathway.
This new project is based on using genetic variants residing in genes associated with HDL-C (as reported by the Global Lipid Consortium) and testing their association with HDL related NMR metabolites. In addition, we are extending our analyses to test the association between HDL related genetic variants and scores developed from HDL metabolites which were generated using factor analysis, in order to determine whether any consistencies exist between the direction of effect and factors of HDL metabolites.